Dissecting the impact of chemotherapy on the human hair follicle: A pragmatic in vitro assay for studying the pathogenesis and potential management of hair follicle dystrophy

Eniko Bodó, Desmond J. Tobin, York Kamenisch, Tamás Bíró, Mark Berneburg, Wolfgang Funk, Ralf Paus

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Chemotherapy-induced alopecia represents one of the major unresolved problems of clinical oncology. The underlying molecular pathogenesis in humans is virtually unknown because of the lack of adequate research models. Therefore, we have explored whether microdissected, organ-cultured, human scalp hair follicles (HFs) in anagen VI can be exploited for dissecting and manipulating the impact of chemotherapy on human HFs. Here, we show that these organ-cultured HFs respond to a key cyclophosphamide metabolite, 4-hydroperoxycyclophosphamide (4-HC), in a manner that resembles chemotherapy-induced HF dystrophy as it occurs in vivo: namely, 4-HC induced melanin clumping and melanin incontinence, down-regulated keratinocyte proliferation, massively up-regulated apoptosis of hair matrix keratinocytes, prematurely induced catagen, and up-regulated p53. In addition, 4-HC induced DNA oxidation and the mitochondrial DNA common deletion. The organ culture system facilitated the identification of new molecular targets for chemotherapy-induced HF damage by microarray technology (eg, interleukin-8, fibroblast growdi factor-18, and glypican 6). It was also used to explore candidate chemotherapy protectants, for which we used the cytoprotective cytokine keratinocyte growth factor as exemplary pilot agent. Thus, this novel system serves as a powerful yet pragmatic tool for dissecting and manipulating the impact of chemotherapy on the human HF.

Original languageEnglish (US)
Pages (from-to)1153-1167
Number of pages15
JournalAmerican Journal of Pathology
Volume171
Issue number4
DOIs
StatePublished - Oct 2007

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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